chemoprevention therapy in treating patients at high risk of developing multiple myeloma

Conditions: Multiple Myeloma and Plasma Cell Neoplasm

Summary: rationale: chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. dehydroepiandrosterone and clarithromycin may be effective in preventing multiple myeloma. purpose: randomized phase ii trial to compare the effectiveness of dehydroepiandrosterone with that of clarithromycin in treating patients who may be at a high risk of developing multiple myeloma.

objectives: * determine whether dehydroepiandrosterone (dhea) or clarithromycin causes a significant reduction in bone marrow plasmacytosis, serum and/or urine m protein or bence jones protein, and surrogate endpoint biomarkers in patients with monoclonal gammopathy of undetermined or borderline significance. * determine whether differences in interleukin-1-beta (il-1-beta) expression and il-1-beta dependent biomarkers (adhesion molecule expression and serum interleukin-6 levels) are useful surrogate endpoint biomarkers in these patients. * determine whether differences in ploidy, proliferative index, nuclear pleomorphism index, circulating monoclonal plasma cells, th1/th2 ratios, serum s-interleukin-6r (sil-6r) levels, interleukin-6 and sil-6r expression, or plasma cell apoptosis assay are useful surrogate endpoint biomarkers in these patients. * determine the effects of these treatment regimens on the quality of life of these patients. outline: this is a randomized, double-blind, placebo-controlled study. patients are stratified according to disease (monoclonal gammopathy of undetermined significance vs monoclonal gammopathy of borderline significance) and monoclonal protein abnormality (igg vs iga). patients are randomized to 1 of 4 treatment arms. * arm i: patients receive oral dehydroepiandrosterone (dhea) once daily. * arm ii: patients receive oral clarithromycin once or twice daily. * arm iii: patients receive oral placebo once daily. * arm iv: patients receive oral placebo twice daily. treatment continues for 6 months in the absence of disease progression or unacceptable toxicity. quality of life is assessed at baseline, 6 months, 12 months, and then at disease progression. patients are followed every 3 months for 1 year and then every 6 months for 1.5 years. projected accrual: a total of 75 patients (25 per treatment arms i and ii and 25 between arms iii and iv) will be accrued for this study within 2.5 years.

Eligibility criteria:
disease characteristics: * new or prior diagnosis of 1 of the following: * monoclonal gammopathy of undetermined significance * bone marrow plasma cells of less than 10% * monoclonal gammopathy of borderline significance * bone marrow plasma cells of 10-30% * serum igg or iga at least 1.5 g/dl * bone marrow plasmacytosis no greater than 30% * no multiple myeloma, amyloidosis, or b-cell neoplasm * no evidence of bone lesions * prostate-specific antigen less than 4 ng/ml patient characteristics: age: * 18 and over performance status: * ecog 0-1 life expectancy: * not specified hematopoietic: * see disease characteristics hepatic: * bilirubin no greater than 1.5 times upper limit of normal (uln) (unless history of gilbert's disease) * ast and alt no greater than 1.5 times uln (unless history of gilbert's disease) renal: * creatinine no greater than 1.8 mg/dl cardiovascular: * no new york heart association class iii or iv heart disease * no prior thromboembolic event within the past 5 years other: * no prostate cancer or clinically significant benign prostatic hypertrophy * no prior malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix * no malignancy suspected on mammogram * no hypersensitivity to dhea, clarithromycin, or any macrolide antibiotic (e.g., erythromycin) * no insulin-dependent diabetes * not pregnant or nursing * negative pregnancy test * fertile patients must use effective barrier method of contraception prior concurrent therapy: biologic therapy: * not specified chemotherapy: * not specified endocrine therapy: * at least 30 days since prior dhea or other steroids that may affect m protein radiotherapy: * not specified surgery: * not specified other: * at least 30 days since prior clarithromycin * at least 30 days since any other prior agents that may affect m protein * no concurrent cisapride, terfenadine, pimozide, astemizole, or loratadine

Keywords: multiple myeloma